T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive T-cell malignancy that is most common in children and adolescents.
Leukemic transformation of thymocytes is caused by the cooperation of mutations that affect proliferation, survival, cell-cycle, and T-cell differentiation. Molecular analyses have identified a large number of T-ALL specific genetic alterations including deletion of CDKN2A (p16), ectopic expression of transcription factors, episomal amplification of ABL1, and mutation of NOTCH1.1-4 
Inhibition of NOTCH1 activation by treatment with a gamma-secretase inhibitor (GSI) was shown to inhibit the proliferation of the T-ALL cell lines ALL-SIL and RPMI-8402.4 The MYB gene encodes a nuclear transcription factor that is implicated in proliferation, survival and differentiation of hematopoietic progenitor cells.10 Proper levels of MYB expression were shown to be important during several steps of hematopoietic cell development, and overexpression of MYB impairs hematopoietic differentiation.11, 12 A viral form of the MYB gene is present in the avian myeloblastosis and E26 viruses, and the Myb gene is a frequent target of retroviral insertions in myeloid, B- and also T-cell leukemias.8, 13, 14 To date, however, no abnormalities affecting MYB have been identified in human T-ALL and it has not been documented that inhibitors of MYB alone, or in combination with inhibitors of NOTCH1, affect differentiation, proliferation and/or survival of T-ALL cells.